Surfaces that are intended to be touched by human operators or contacted with human tissue, accordingly, will be exposed to the microorganisms either typically or incidentally found on skin and mucosal tissue. Of particular concern are surfaces that will be in contact with tissue for extended periods of time where bacteria can colonize, grow, and potentially form a biofilm. These surfaces are notorious for causing infection. For example, venous access catheters, urinary catheters, endotracheal tubes, nasal gastric tubes, feeding tubes and other devices which enter a natural or created orifice are at risk for causing infections which can have very serious consequences for the patient. Biofilms are structured communities of microorganisms encased in an extracellular polymeric matrix that typically are tenaciously adhered to the surface of biomaterials and host tissue. Bacterial biofilms are a significant issue in the development of materials that are exposed to aqueous and body fluids for prolonged periods for several different application areas: medical devices, filtration systems for food processing and other industrial applications, coatings for marine structures and other anti-fouling applications. Bacteria living in a biofilm are considerably more resistant to host defenses and antibiotic or antimicrobial treatments, when compared to “free” pathogens, and thereby increase the potential for infections during the use of in-dwelling and other tissue contacting devices.
Biofilms are believed to have a significant role in catheter associated urinary tract infections (CAUTI) and ventilator associated pneumonia (VAP). CAUTIs comprise the largest percentage of hospital acquired infections (HAIs) and are the second most common cause of nosocomial bloodstream infections. VAP has the highest morbidity of all HAIs, as roughly 15% of patients with VAP will die. VAP may also be the most expensive HAI to treat ($20,000-$50,000 per episode), and has an incident rate between 25% and 40% for patients having longer term urinary catheters.
By way of example, and without wishing to be bound by theory, biofilm formation on urinary catheter surfaces may proceed as follows: 1) The catheter surface is initially colonized by bacteria (some of them urease-producing bacteria) originally present on the periurethral skin and able to migrate into the bladder between the epithelial surface of the urethra and the catheter once the catheter is inserted. The adsorption of these cells to the catheter surface may be facilitated by the formation of an organic conditioning film made up largely of adsorbed proteins. 2) A bacterial biofilm community forms, encased primarily by a matrix of bacterial exopolysaccharide. The pioneer biofilm forming bacteria that initially cause urinary tract infections (UTIs) are typically S. epidermidis, E. coli or E. faecalis, with E. coli the overwhelming cause of CAUTI. At longer catheterization times, other species appear including P. aeruginosa, P. mirabilis, and K. pneumoniae. These latter stage bacteria are more difficult to treat with antibiotics while the catheter is in place. 3) The presence of a growing biofilm, including bacterial species that are capable of producing urease, leads to an elevation of the urine's pH due to the action of urease on urea. 4) As the urine becomes alkaline, calcium phosphate and magnesium ammonium phosphate crystals precipitate and accumulate in the biofilm matrix growing on the catheter surface. 5) Continued crystal formation in the alkaline urine and continued growth of the biofilm lead to severe encrustation and eventually blockage of the device which necessitates re-catherization of the patient. Thus, preventing colonization and biofilm formation on the catheter could play a large role preventing CAUTIs as well as blood stream infections (BSIs).
Attempts have been made to provide surfaces that are inherently antimicrobial, either by composition or use of antimicrobial drug delivery systems. These surfaces can be insufficiently effective in reducing biofilm formation for three important reasons: 1) when used as a delivery system, antimicrobial or active agents may be exhausted well before the end of the service lifetime of the medical article; 2) the surface antimicrobial properties are eventually impaired as dead cells, the high organic load in the urethra, and other adsorbed biomaterial mask the antimicrobial properties of that surface; and 3) antimicrobial agents in the catheter material or in an external coating fail to elute sufficiently.
Thus surfaces of certain medical devices and particularly those that are in contact with moist mammalian tissue provide a suitable home for bacteria, fungi, algae, and other single celled microrganisms which thrive and propagate based on the availability of appropriate amounts of moisture, temperature, nutrients, and receptive surfaces. As these organisms metabolize, they produce chemical by-products. These chemicals can be toxins and/or pyrogens. Thus, these microorganisms, as well as their metabolic products can pose serious health risks to users ranging from minor tissue irritation to more serious toxic response and disease.
Further complicating the matter is that most venous access catheters, urinary catheters, endotracheal tubes, NG tubes and other patient contact devices are made from flexible and often elastomeric plastics. Furthermore, these devices can be moved and flexed repeatedly during insertion and use. It can be exceedingly difficult to adhere to such surfaces.
There exists a need for simple means to prevent the colonization of articles by microorganisms and/or a means to reduce the number of living microorganisms that become disposed on a surface in a manner that will durably adhere to flexible and elastomeric substrates.